Absorptive Site Blood Flow Research Articles

Modulation of hemorrhagic shock by intestinal mucosal NG-nitro-L-arginine and L-arginine in the anesthetized rat.

Maintaining intestinal function protects against shock of various origins. Nitric oxide (NO) can protect tissues. The present research examined whether the presence of 50 microM NG-nitro-L-arginine (NOLARG), a nitric oxide synthase (NOS) inhibitor, or L-arginine (LARG), the substrate of NOS, in the jejunal lumen of the anesthetized rat could affect the progress of hemorrhagic shock. The jejunal lumen was perfused with saline containing 14C-inulin and 3H2O to measure net H2O absorption and absorptive site blood flow (ASBF). Luminal NOx (NO3- +NO2-) secretion into the gut effluent and blood pressure (BP) were also measured. The animals were bled to and maintained at 40 mmHg for 60 min and then reinfused. Survival time was significantly decreased in luminally-perfused NOLARG animals, but was significantly increased in LARG perfused animals. Most deaths occurred during the hemorrhage periods. Animals perfused with LARG through the ileal lumen required significantly less blood to be reinfused to maintain blood pressure during the hemorrhage periods. There were not significant differences in BP among surviving animals. Net H2O absorption and ASBF were significantly decreased only in NOLARG-perfused animals in the period just before and after reinfusion. There were no significant differences in luminal NOx secretion among the groups. Thus, intestinal mucosal NOS substrates or antagonists modulate the progress of hemorrhagic shock, but the mechanism was not defined in these experiments.

Effect of intestinal blood flow on absorptive site blood flow and lysine absorption as examined in situ in Holstein calves.

Total blood flow from an intestinal segment (TBF) was altered to determine effects on blood flow at the absorptive site (ASBF) and lysine absorption. Venous blood flow was restricted using a peristaltic pump to 20, 35, 50, 65, and 80% of the initial unrestricted rate. Lysine absorption and ASBF were determined from recovery of 14C and 3H in blood from intestinally perfused [14C]L-lysine and 3H2O, respectively. Fluid flux in the intestinal lumen was estimated from the difference in polyethylene glycol concentrations in luminal infusate and effluent. Restriction of TBF proportionally reduced ASBF, which composed 3 to 6% of TBF. Lysine absorption was reduced linearly during reduction of TBF. Fluid absorption varied among calves but was independent of TBF. Differences between loss of radioactive marker from perfusate and recovery in blood suggested a loss of 3H2O from the intestinal segment that was independent of TBF. Changes in blood flow to the small intestine may affect nutrient absorption in ruminants.

Physiological and Anatomical Factors Affecting Intestinal Drug Absorption and Absorption Enhancement by Modifying Their Factors.

As physiological and anatomical factors affecting intestinal drug absorption, unidirectional water flow, solvent drag, absorptive site blood flow and electrophysiological parameters such as membrane resistance and capacitance were examined. Effects of some absorption enhancers on the two absorption pathways, the transcellular and paracellular pathways, were also examined from the alteration of the above factors. One of the effective enhancers, sodium caprate (C10), increased the following absorption parameters for the paracellular pathways : (i) the equivalent pore radius which was obtained by the water absorption ; (ii) the permeabilities of water-soluble nonelectrolytes and ionic drugs ; (iii) junctional resistance and basolateral membrane capacitance which were obtained by impedance analysis. The C10 effects on the trancellular pathway were found in the membrane perturbation which was obtained by fluorescence polarization. For the action mechanism of C10 in the paracellular pathways, the C10 effect on the physiological regulation of membrane, stimulation of C10 to contraction of perijunctional actomyosin ring, is now under investigation.

Pharmacokinetic Modelling of the Effect of Activated Charcoal on the Intestinal Secretion of Theophylline, using the Isolated Vascularly Perfused Rat Small Intestine

The effect of activated charcoal administration on the secretion of theophylline from the blood into the intestinal lumen has been examined by use of the rat isolated vascularly perfused small intestine. A closed two compartment model was used to analyse the vascular and luminal concentration-time curves obtained. An equation was derived to calculate the time-dependent intestinal clearance. From control experiments it was concluded that theophylline is secreted by a diffusional transport system through the intestinal wall. The intestinal clearance declined rapidly with time as a result of the concomitant increase in luminal theophylline concentration. After 120 min a steady state between the vascular and luminal perfusate was established. Administration of activated charcoal in the lumen had a profound effect on the kinetics of the drug. The vascular steady state concentration was depressed dramatically. The theophylline clearance remained nearly constant with time, because the blood to lumen concentration gradient was maximized. The maximal value for the intestinal theophylline clearance was estimated to be 0.88 mL min-1 and it equalled the value for the intestinal blood flow at the absorptive site. By use of the concept of absorptive site blood flow, the maximal effect of charcoal on systemic theophylline clearance could be adequately predicted for rats, dogs and man. Activated charcoal administration is only useful to enhance the systemic clearance of drugs or toxicants if that clearance is of the same order of magnitude as the absorptive site blood flow or lower.

Relationship between antipyrine absorption and blood flow rate in rat jejunum, ileum, and colon.

The appearance rate of antipyrine in intestinal venous blood was measured in anesthetized rats during perfusion (0.2 ml/min) of a buffered solution with 1 mmol/l labeled antipyrine through a jejunal, ileal, or colonic segment (length: 2-5 cm). When the blood flow rate was increased from 0.9-1.2 to 1.6-2.0 ml min-1 g-1 by raising the systemic blood pressure from 80 to 130 mm Hg, the absorption of antipyrine increased only in the colon. Stepwise reduction of the blood flow rate from 1.4-1.7 to 0.2-0.3 or stepwise raise from 0.2-0.3 to 1.4 ml min-1 g-1 by constriction or release of the mesenteric artery decreased or increased the absorption rate of antipyrine. The relation between absorption and flow rate can be described by curves which ascend at low and level off into a horizontal section at high flow rates. At the same blood flow rate the regional absorption rate decreased in the order jejunum, ileum, and colon with the largest step between ileum and colon. Model analysis yielded the following results for jejunum, ileum, and colon, respectively: permeability-surface area product 0.083, 0.074, and 0.037 ml min-1 g-1; fraction of absorptive site blood flow rate 0.24, 0.19, 0.08. The differences can be attributed mainly to the change of the surface area from jejunum to ileum and colon.

Cardiovascular and flux relationships in canine ileum.

Blood flow and pressure in denerved ileum of anesthetized dogs were altered by occlusion of the mesenteric artery or vein or by infusion of intra-arterial sodium nitroprusside (0.015-1.5 mg/min). Unidirectional Na and H2O fluxes were measured and absorptive site blood flow was estimated from the clearance of tritiated H2O. Net Na and H2O absorptions were reduced by mesenteric venous or arterial occlusion. Net secretion occurred with mesenteric venous occlusion. Nitroprusside reduced net absorption only at an infusion rate of 0.15 mg/min. The absorptive Na and H2O fluxes were reduced by both mesenteric venous or arterial occlusion, with venous occlusion being more effective. Nitroprusside reduced the absorptive Na flux at an infusion rate of 0.15 mg/min but not the absorptive H2O flux. The secretory flux of Na was increased by mesenteric venous occlusion but reduced by arterial occlusion and not changed by nitroprusside infusion. The secretory H2O flux was decreased by moderate degrees of mesenteric venous occlusion but was unchanged at greater levels. Arterial occlusion decreased secretory H2O fluxes. Nitroprossude infusion increased secretory H2O fluxes at an infusion rate of 0.015 mg/min. The absorptive and secretory Na and H2O fluxes were significantly correlated with absorptive site blood flow plus estimated capillary pressure. Absorptive site blood flow was primarily responsible for changes in absorptive fluxes and estimated capillary pressure for changes in secretory fluxes. Absorptive site blood flow affected the secretory and absorptive fluxes of H2O more equally than the Na fluxes.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow distribution, villous tissue osmolality and fluid and electrolyte transport in the cat small intestine during regional hypotension.

The hemodynamic reactions of the parallel coupled vascular circuits in the cat small intestine were studied before, during and after a two-hour period of intestinal hypotension induced by lowering the intestinal arterial inflow pressure by partially occluding the superior mesenteric artery during a continuous stimulation of the postganglionic nerves to the small intestine. Furthermore, fluid and electrolyte transport and villous tissue osmolality were measured. A histological examination of biopsies taken during and after the hypotensive period was also carried out. The animals were divided into two groups (undamaged and damaged) according to the histological appearance of the intestinal mucosa. The hemodynamic reactions were investigated with a method that made it possible to study total intestinal, absorptive site ("villous"), nonabsorptive site ("crypt") and muscle layer blood flow. Total intestinal blood flow was lower in the damaged group than in the undamaged group during the arterial hypotension. However, absorptive site blood flow was similar in the two groups. Consequently, a significantly larger fraction of blood flow was distributed to the "villi" in the damaged group. Moreover, absorptive site red blood cell flow was only slightly reduced despite the development of mucosal ulcerations. These findings are discussed in relation to the pathophysiology of the mucosal lesions. Net fluid, net sodium and net chloride absorption was unchanged in the undamaged group whereas in the damaged group a marked decrease was observed after lowering the perfusion pressure. The decrease in net sodium absorption was due to a decrease in the lumen to tissue transport of sodium. Thus, the capacity of the small intestine to absorb fluid and electrolytes is unchanged even during a marked arterial hypotension with a pronounced decrease of intestinal blood flow as long as no mucosal damage has developed.

Effects of hemorrhage on intramural blood flow distribution, villous tissue osmolality and fluid and electrolyte transport in the cat small intestine

The hemodynamic response in the parallel-coupled vascular sections of the cat small intestine were studied before, during and after a two hour period of hemorrhage (about 30 per cent of estimated blood volume). Fluid and electrolyte transport and villous tissue osmolality were also measured. Biopsies for histology were taken at the end of all experiments. The animals were divided in two groups, undamaged and damaged, according to the degree of mucosal damage observed. The hemodynamic reactions were investigated with a method that made it possible to study total intestinal, absorptive site ("villous"), nonabsorptive site ("crypt") and muscle layer blood flows. Total intestinal blood flow was lower in the damaged as compared to the undamaged group during hypovolemia. No difference in absorptive site blood flow was observed between the two groups during hypovolemia. Furthermore, no decrease of red blood cell flow in the "villi" was recorded in either group after hemorrhage. Consequently, mucosal lesions developed despite an unchanged oxygen transport capacity to the villi. The pathophysiology of the mucosal lesions is briefly discussed. Net fluid and sodium absorption was after hemorrhage increased in the undamaged group reflecting a decrease in the tissue to lumen transport of sodium. After retransfusion net fluid and sodium absorption returned to control. In the damaged group, however, net fluid and sodium absorption was decreased after hemorrhage. The increased rate of fluid and electrolyte transport observed in the undamaged small intestine after hemorrhage, is proposed to be an important mechanism for fluid replacement after hemorrhage.

Morphine-neural interactions on canine intestinal absorption and blood flow.

Intestinal Na and H2O fluxes and blood flow were determined in extrinsically denervated or innervated ileum of fed dogs during intra-arterial (0.2, 2, 20 micrograms min-1) or intraluminal (4, 40, 400 micrograms ml-1) morphine sulphate infusion. 3H2O and 22Na were used to determine unidirectional fluxes and 3H2O clearances were used to determine total segmental and absorptive site blood flow. Net Na and H2O absorption decreased with time in innervated gut segments but were unchanged in denervated segments. Intra-arterial morphine prevented the decrease in net Na and H2O absorption in innervated segments due to increases in unidirectional absorptive fluxes. Intra-arterial morphine did not affect absorption in denervated segments. Intraluminal morphine increased net Na and H2O absorption from both innervated and denervated ileal segments due to increases in the unidirectional absorptive fluxes. Absorptive site blood flow was linearly related to unidirectional absorptive Na fluxes in each group although not with the same slopes. The increment in absorptive site blood flow vs. absorptive Na flux was greatest with luminal morphine, intermediate with intra-arterial morphine and in denervated segments without morphine and least in innervated segments. It was concluded that intra-arterial morphine inhibits an antiabsorptive effect of extrinsic nerves and that intraluminal morphine promotes an absorptive effect which could be direct or mediated through intrinsic nerves.

Effects of atropine and guanethidine on canine intestinal absorption and blood flow

The possibility of tonic autonomic control over intestinal Na and H 2O absorption and whether the cardiovascular system was involved was tested by administration of atropine or guanethidine. 3H 2O and 22Na in saline perfused through the lumen were used to calculate unidirectional fluxes and total and absorptive site blood flow in canine ileum. Both atropine and guanethidine had qualitatively similar effects on absorption and blood flow with atropine being quantitatively greater. Net Na and H 2O absorption were not increased significantly but their absorptive and secretory unidirectional fluxes were increased significantly. Total blood flow was not affected but absorptive site blood flow was increased and resistance decreased. The absorptive site blood flow was correlated with the absorptive Na fluxes similarly in all groups. The secretory fluxes of Na and H 2O were correlated with estimated capillary pressure when all three groups were considered together. It was concluded that there is tonic cholinergic control over intestinal absorption which is mediated, in part, through cardiovascular effects. The findings were consistent with tonic parasympathetic activity having primarily a direct effect on gut absorption and blood flow but tonic sympathetic activity primarily modulating the direct effects of other regulatory mechanisms.

Influence of bloodflow on the absorption of theophylline from the jejunum of the rat.

The influence of the jejunal bloodflow on the absorption of theophylline was investigated. The bloodflow through a segment under investigation was varied by changing the systemic blood pressure by means of a donor blood infusion into the jugular vein or by an infusion of isoprenaline or levarterenol into a femoral vein, and was measured by collecting the venous outflow from the intestinal segment. Above a bloodflow of approximately 0.40 µl/min/cm the flux/ flow ratio is reduced, and it is proposed that above this flow the intestinal epithelium provides the rate limiting step in the absorption of theophylline. When the bloodflow was held low for a prolonged time, the flux of theophylline decreased. The absorptive site bloodflow was calculated to be 18 % of the total bloodflow through the segment under investigation.

Intrinsic regulation of functional blood flow and water absorption in canine colon.

1. Autoregulation of total and absorptive site blood flow and H2O fluxes were studied in canine colon during arterial pressure decreases and venous pressure elevations. 2. Reductions in arterial pressure caused proportional decreases in total colonic blood flow indicating no autoregulatory ability. In contrast, absorptive site blood flow was constant over an arterial pressure range of 40-140 mmHg but decreased sharply below 40 mmHg. 3. Venous pressure elevation decreased total blood flow and increased resistance but had no effect on absorptive site blood flow over a range of 0-30 mmHg. 4. Net H2O absorption was unchanged by alteration of arterial or venous pressure but the unidirectional H2O fluxes decreased with arterial pressure reduction and were unchanged by venous pressure elevation. 5. Adenosine infusion increased total and absorptive site blood flow and the unidirectional H2O fluxes yet had no effect on net H2O flux. 6. It was concluded that absorptive site blood flow is very well autoregulated in the colon but total blood flow is not. Net H2O absorption is maintained during decreased blood flow by maintenance of blood flow to the mucosa and by decreasing the back flux of H2O across the mucosa.

Effects of pentagastrin on intestinal absorption and blood flow in the anaesthetized dog.

1. Pentagastrin (1, 10 micrograms/min) was infused I.V. into fed and fasted anaesthetized dogs and the intestinal absorption of NaCl and H2O and blood flow were determined. The influence of pentagastrin-induced cardiovascular changes on absorption was investigated. 2. 22Na and 3H2O were used to determine the unidirectional Na and H2O fluxes from saline perfused through the ileal lumen and the clearances of 3H2O were used to calculate total and absorptive site blood flow. 3. Ileal absorption of Na and H2O was reduced by 10 micrograms/min pentagastrin due primarily to significant increases in the secretory flux of Na and decreases in the absorptive flux of H2O in both fed and fasted animals. 4. Neither total intestinal blood flow, arterial nor mesenteric vein pressure were changed by pentagastrin but absorptive site blood flow was decreased in fasted but not in fed dogs. 5. Pretreatment with atropine reduced the effects of pentagastrin but pretreatment with guanethidine potentiated the effects of pentagastrin. 6. Absorptive site blood flow was positively linearly correlated with the absorptive fluxes of both Na and H2O. The relationships between the secretory fluxes of Na and H2O and estimated capillary pressure were changed from a positive relationship in control periods to a less positive or negative relationship following pentagastrin. 7. It was concluded that pentagastrin reduces intestinal absorption through both a cardiovascular effect and an effect on the intestinal epithelium. Also, there is a strong autonomic component in the effects of pentagastrin on intestinal absorption.

Effects of morphine on canine intestinal absorption and blood flow.

1 Intestinal absorption and blood flow were determined in anaesthetized fed or fasted dogs following rapid intravenous injections of morphine (0.01, 0.1, 1 mg/kg). 2 3H2O and 22Na were used to determine the unidirectional fluxes of Na+ and H2O from saline perfused through the ileal lumen and the clearances of 3H2O were used to determine total and absorptive site blood flow. 3 Net Na+ and H2O absorption were increased at each dose of morphine in fed but not in fasted dogs, due primarily to increased absorptive fluxes. 4 Arterial pressure was decreased by morphine but mesenteric vein pressure was little affected. Absorptive site blood flow was increased by morphine due to decreased blood flow resistance but total blood flow resistance was little affected by morphine. 5 The absorptive fluxes of Na+ and H2O were correlated with absorpitve site blood flow in both fed and fasted animals. The secretory fluxes of Na+ and H2O were correlated with estimated capiliary pressure in fasted dogs but morphine decreased the the secretory fluxes at a given capillary pressure in dogs which had been fed. 6 Naloxone (0.12 mg, i.v.) reversed the effects of morphine. The effects of morphine on the gut were reversed more slowly than on systemic blood pressure. 7 It was concluded that morphine can increase net absorption in fed dogs by a selective increase in intestinal absorptive site blood flow and thus increase absorptive fluxes by a washout effect but that there is also an epithelial effect, sensitized by feeding, which reduces the secretory fluxes of Na+ and H2O.

Effects of vasoactive intestinal polypeptide on intestinal absorption and blood flow.

1. Intestinal absorption and blood flow in anaesthetized dogs was determined after I.V. infusion of vasoactive intestinal polypeptide (VIP) (1.75-175 ng/min) to determine the contribution of the cardiovascular changes to transport. 2. 22Na and 3H2O were utilized to determine the unidirectional fluxes of Na and H2O from saline perfused through the ileal lumen and the clearances of 3H2O were used to determine total and absorptive site blood flow. 3. Net Na and H2O absorption were reversed to secretion by VIP at 175 ng/min due to a significant decrease in unidirectional absorptive fluxes and smaller increases in secretory fluxes. 4. Arterial pressure and absorptive site blood flow were reduced in proportion to the changes in Na and H2O fluxes. 5. Total and absorptive site blood flow decreased and the blood flow resistances increased. 6. Prior treatment with guanethidine to suppress sympathetic effects did not greatly affect the responses to VIP. Prior treatment with atropine to suppress cholinergic effects inhibited most of the effects of VIP. 7. Absorptive site blood flow was linearly related to absorptive fluxes of Na and H2O but with different slopes for results from atropinized dogs as compared to those from dogs given VIP alone or VIP plus guanethidine. 8. It was concluded that VIP reduces gut absorption through a generalized cardiovascular effect and also through a mechanism which depends on the release of ACh by the gut.

Effects of glucagon on canine intestinal sodium and water fluxes and regional blood flow.

1. Glucagon (0-05 or 0-5 microng/kg. min) was infused into a mesenteric artery of a canine ileal segment from which transport was measured (direct infusion) or into a mesenteric artery of an adjacent non-perfused segment (indirect infusion). Unidirectional Na and H2O fluxes and arterial and mesenteric vein pressures and total and absorptive site blood flows were measured. 2. Direct glucagon infusion increased the absorptive and secretory fluxes of Na and H2O and absorptive site blood flow, and decreased absorptive site resistance and arterial and mesenteric vein pressure. Indirect glucagon infusion had the opposite effects. 3. Neither the direct arterial infusion of histamine (0-1-53 microng/kg. min) nor the I.V. infusion of glucose (0-2 g/min) or insulin (0-1 micron/kg) or glucose plus insulin, mimicked the effects of glucagon. 4. The unidirectional secretory and absorptive fluxes of both Na and H2O were linearly related to the calculated capillary pressure during glucagon infusion. 5. It was concluded that the effects of glucagon on gut transport were due to effects exerted through the cardiovascular system.

The effect of saline and hyperoncotic dextran infusion on canine ileal salt and water absorption and regional blood flow.

1. The unidirectional Na and H2O fluxes, vascular pressures and total and absorptive site blood flows in the canine ileum were determined before and during I.V. saline infusion and subsequent I.V. infusion of hyperoncotic dextran. The intestinal perfusion solutions were isotonic saline or isotonic saline and mannitol, but the effects of I.V. saline or I.V. hyperoncotic dextran infusion were generally the same for both luminal solutions. 2. Continuous I.V. infusion of saline caused a continuous increase in the unidirectional flux of Na and H2O into the ileal lumen, an increase in total blood flow, and an increase in venous pressure. 3. The net absorption of Na and H2O was decreased by I.V. saline infusion. 4. The unidirectional fluxes of Na and H2O out of the lumen, arterial pressure, and absorptive site blood flow were not affected by I.V. saline infusion. 5. I.V. hyperoncotic dextran infusion reversed most of the effects of saline infusion. 6. The unidirectional fluxes of Na and H2O into the lumen were significantly correlated with Starling forces during I.V. saline infusion. 7. It was concluded that intestinal transport of salt and water was subject to regulation by physical forces at the capillary level.